TLDR The structure of SRD5A reveals how it reduces steroids, aiding drug design for related health conditions.
The study reported the crystal structure of the steroid 5α-reductase (SRD5A) from Proteobacteria bacterium, revealing a conserved mechanism for NADPH-mediated steroid reduction. The structure, resolved at 2.0 Å, showed that PbSRD5A, which shares significant sequence similarity with human SRD5A1 and SRD5A2, exists as a monomer with seven transmembrane segments. These segments form a hydrophobic cavity for steroid binding and coordinate with NADPH through hydrogen bonds. The findings provided insights into substrate recognition and could aid in designing specific therapeutic molecules targeting SRD5As to treat conditions like benign prostatic hyperplasia, alopecia, prostatic cancer, and infertility.
Cited in this study
6 / 6 results
39 citations
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April 2018 in “Hormones” No consistent link between genotype and phenotype in 5-α-Reductase type 2 deficiency.
218 citations
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January 2012 in “Advances in Urology” The document concludes that the 5 alpha-reductase enzymes are important in steroid metabolism and related to various human diseases, with inhibitors used to treat conditions like male pattern baldness and prostate issues.
260 citations
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July 2010 in “Cell” Mutations in the SRD5A3 gene cause a new type of glycosylation disorder by blocking the production of a molecule necessary for protein glycosylation.
49 citations
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January 2004 in “Journal of steroid biochemistry and molecular biology/The Journal of steroid biochemistry and molecular biology” Selective non-steroidal inhibitors of 5α-reductase type 1 can help treat DHT-related disorders.
46 citations
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March 2001 in “Journal of endocrinological investigation” 5α-reductase inhibitors, like finasteride and dutasteride, effectively treat BPH, male baldness, and hirsutism, with potential for acne and prostate cancer prevention.
25 citations
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September 1998 in “The Journal of Steroid Biochemistry and Molecular Biology” Finasteride inhibits enzyme activity in rhesus macaques, suggesting they're useful for evaluating similar drugs.
